简介：摘要目的探讨1个双耳极重度感音神经性聋患儿的致病基因变异类型，明确可能的遗传学病因，并对该家系进行产前诊断。方法应用高通量测序方法对先证者进行415个遗传性耳聋相关基因的序列检测，使用多重连接探针扩增(multiplex ligation-dependent probe amplification，MLPA)方法对测序结果进行验证并对先证者父母和胎儿进行检测。结果先证者DNA中检测到与X染色体连锁耳聋2型(deafness X-linked 2，DFNX2)相关的POU3F4基因完全缺失变异，按照美国医学遗传学与基因组学学会遗传变异分类标准与指南进行致病性评级，该变异为致病性变异(PVS1+PM2+PP4)，先证者母亲和胎儿均为POU3F4基因杂合缺失变异携带者，先证者父亲POU3F4基因拷贝数正常。结论POU3F4基因缺失变异是一个基因功能丢失变异，可能为该家系耳聋发生的遗传学病因，可用于指导家系进行产前诊断，胎儿产后听力正常，与产前诊断结果一致。

简介：摘要目的观察重复经颅磁刺激(rTMS)对抑郁小鼠前额叶皮质和海马区嘌呤2X7受体(P2X7R)及胶质纤维酸性蛋白(GFAP)表达的影响。方法将30只C57BL/6小鼠分为对照组(10只)和造模组(20只)。对照组小鼠群居饲养(5只/笼)，造模组小鼠在出生21 d后通过断奶独居(1只/笼)饲养6周制作慢性抑郁小鼠模型。采用随机数字表法将16只制模成功小鼠分为模型组及rTMS组，每组8只小鼠。rTMS组小鼠给予10 Hz rTMS干预，每周干预5 d。于rTMS干预4周后观察各组小鼠抑郁样行为改变，并对比各组小鼠前额叶皮质和海马区P2X7R、GFAP表达变化。结果与对照组比较，模型组小鼠蔗糖偏好实验(SPT)中糖水偏好量、旷场实验(OFT)中运动距离均显著减少(P<0.05)，悬尾实验(TST)中静止不动时间显著增加(P<0.05)，前额叶皮质和海马区P2X7R表达水平均明显增加(P<0.05)，GFAP表达水平则显著下降(P<0.05)。与模型组比较，rTMS组SPT糖水偏好量[(75.11±4.58)% vs(65.14±4.87)%]、OFT运动距离[(2289.34±100.16)cm vs (2028.90±178.21)cm]均显著增加(P<0.05)，TST静止不动时间[(78.11±10.89)s vs(101.39±10.38)s]明显缩短(P<0.05)，前额叶皮质和海马区P2X7R表达均明显降低(P<0.05)，GFAP表达则显著增强(P<0.05)。结论rTMS干预能有效改善早期独居小鼠抑郁状态，其治疗机制可能与抑制前额叶皮质和海马区P2X7R表达、促进GFAP表达有关。

简介：摘要目的对一个疑似X-连锁迟发性脊椎骨骺发育不良（spondyloepiphyseal dysplasia tarda，SEDT）的家系进行临床特征分析和致病基因的筛查，并对可疑变异进行分析，为遗传咨询和产前诊断提供实验依据。方法采集家系成员病史，一般体检，关节、脊椎X线片检查；收集该家系成员外周血样，提取样本DNA，采用靶向基因高通量测序方法对先证者DNA全外显子进行测序，并对测序数据进行分析；针对可疑突变，采用PCR和Sanger测序对家系其他成员DNA样本进行验证；提取家系成员外周血淋巴细胞的RNA，RT-PCR扩增致病基因外显子3、4区域，琼脂糖凝胶鉴定扩增片段大小；并采用qPCR检测致病基因的表达。结果根据家系中患者临床表型和脊椎X线片特征，将该家系患者诊断为X-连锁隐性遗传SEDT。全外显子测序检测到先证者转运蛋白复合体亚单位2（trafficking protein particle complex subunit 2，TRAPPC2）基因NM_001011658：c.91A>T（p.K31*）无义突变，其表弟该基因位点也存在相同变异，家系其他无表型成员未检出该变异。患者外周血淋巴细胞RT-PCR结果与家系正常对照的扩增片段相同，表明该变异不影响转录本的剪接。qPCR结果显示，家系患者TRAPPC2的转录水平表达较家系正常对照及正常人对照显著降低。结论发现TRAPPC2基因c.91A>T新无义变异，该变异可以导致TRAPPC2功能丧失，是本家系的致病性变异。

简介：摘要目的探讨Eph受体酪氨酸激酶A2(EphA2)和X连锁凋亡抑制蛋白(XIAP)在膀胱尿路上皮癌组织中的表达以及临床意义。方法收集2015年1月至2020年11月惠州市第六人民医院(南方医科大学附属惠阳医院)和广东医科大学附属医院病理学确诊的72例膀胱尿路上皮癌组织标本和对应癌旁组织，采用免疫组织化学方法检测上述组织中EphA2蛋白和XIAP蛋白表达水平，结合研究对象临床资料进行χ2检验。结果EphA2蛋白在膀胱尿路上皮癌组织中的阳性表达率为62.50%(45/72)，明显高于癌旁组织阳性表达率[16.67%(12/72)]，差异有统计学意义(χ2＝31.623，P<0.01)。XIAP蛋白在膀胱尿路上皮癌组织中的阳性表达率为76.39%(55/72)，明显高于癌旁组织阳性表达率[12.50%(9/72)]，两者差异有统计学意义(χ2＝59.513，P<0.01)。EphA2蛋白表达水平与膀胱尿路上皮癌组织学分化程度、浸润深度、淋巴结转移和TNM分期明显相关(χ2＝6.301、5.217、4.307、4.267，P<0.05)XIAP蛋白表达水平与膀胱尿路上皮癌组织学分化程度、淋巴结转移和TNM分期明显相关(χ2＝5.256、5.840、4.659，P<0.05)。结论在膀胱尿路上皮癌组织中EphA2蛋白和XIAP蛋白呈高表达，EphA2蛋白和XIAP蛋白检测有助于判断膀胱尿路上皮癌的生物学行为。

简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.

简介：AbstractOmicron (B.1.1.529), the fifth variant of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was firstly identified in November 2021 in South Africa. Omicron contains far more genome mutations than any other VOCs ever found, raising significant concerns about its increased transmissibility and immune evasion. Here, we report the importation of the Omicron variant into Beijing, China, in December 2021. Full-length genome sequences of five imported strains were obtained, with their genetic features characterized. Each strain contained 57 to 61 nucleotide substitutions, 39 deletions, and 9 insertions in the genome. Thirty to thirty-two amino acid changes were found in the spike proteins of the five strains. The phylogenetic tree constructed by the maximum likelihood method showed that all five imported genomes belonged to Omicron (BA.1) (alias of B.1.1.529.1), which is leading to the current surge of coronavirus disease 2019 (COVID-19) cases worldwide. The globally increased COVID-19 cases driven by the Omicron variant pose a significant challenge to disease prevention and control in China. Continuous viral genetic surveillance and increased testing among international travellers are required to contain this highly contagious variant.

简介：AbstractAt present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, which has emerged multiple variants and brought a threat to global public health. To analyze the genomic characteristics and variations of SARS-CoV-2 imported into Beijing, we collected the respiratory tract specimens of 112 cases of coronavirus disease 2019 (COVID-19) from January to September 2021 in Beijing, China, including 40 local cases and 72 imported cases. The whole-genome sequences of the viruses were sequenced by the next-generation sequencing method. Variant markers and phylogenic features of SARS-CoV-2 were analyzed. Our results showed that in all 112 sequences, the mutations were concentrated in spike protein. D614G was found in all sequences, and mutations including L452R, T478K, P681R/H, and D950N in some cases. Furthermore, 112 sequences belonged to 23 lineages by phylogenetic analysis. B.1.1.7 (Alpha) and B.1.617.2 (Delta) lineages were dominant. Our study drew a variation image of SARS-CoV-2 and could help evaluate the potential risk of COVID-19 for pandemic preparedness and response.

简介：摘要ObjectiveTo investigate a 5-generation Chinese Han family with PRKAG2 cardiac syndrome resulting from mutations in the PRKAG2 gene encoding the AMP-activated protein kinase (AMPK) gamma 2 subunit and the treatment of myocardial hypertrophy in patients with PRKAG2 cardiac syndrome.MethodIn this study, a 5-generation Chinese Han family (n = 40) with complete atrioventricular block and asymmetric interventricular septal hypertrophy was taken as the research object, and the DNA were obtained from 30 of them (6 patients and 24 normal persons). Objective gene capture combined with high-throughput sequencing technique was used to detect the genes of family members. After the gene diagnosis was confirmed, the cardiac data of patients taking beta-blockers in this family were analyzed retrospectively with the average annual increase in thickness of interventricular septum (expressed in mm/year) as an index.ResultsA total of 6 family members were associated with PRKAG2 (c.905G>A; pR302Q) heterozygous variation. The phenotype of pedigree patients is characterized by complete atrioventricular block and asymmetric interventricular septal hypertrophy, which has high homogeneity. No syncope occurs after implantation of permanent pacemaker, but atrial flutter and atrial fibrillation occur. The 5 patients with PRKAG2 cardiac syndrome in the family took beta-blockers for a long time, and the progress of cardiac hypertrophy was significantly delayed.ConclusionsOur results suggest that the possibility of PRKAG2 mutations should be considered in patients with complete atrioventricular block and asymmetric interventricular septal hypertrophy, and that prompt implantation of pacemakers and long-term use of beta blockers may improve the prognosis of PRKAG2 cardiac syndrome patients.

简介：摘要长期以来，人们一直认为2型糖尿病（T2DM）是一种终身性疾病。近年的临床实践显示，一些T2DM患者在采取某些干预措施后可停用降糖药而血糖仍处于正常或接近正常水平，目前多数学者用“缓解”来描述T2DM患者这种代谢持续改善至接近正常的状态。该文对T2DM缓解的概念和判断标准、实现T2DM缓解的策略、T2DM缓解的影响和预测因素进行介绍，并阐述诱导T2DM缓解的可能机制。T2DM缓解具有重要的临床意义，不仅使患者在一段时间内免于药物治疗，而且可降低患者并发症的发生风险，针对缓解机制的研究还有望衍生出新的干预靶点，但该领域仍存在若干需要解决的问题。临床上对已经缓解的T2DM患者仍不能放松管理，需要定期复查，如患者血糖超过控制标准应按照指南及时启动相应的治疗。

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简介：摘要非酒精性脂肪性肝病（NAFLD）和2型糖尿病（T2DM）十分常见，两者常常互为因果。大量流行病学研究结果显示NAFLD显著增加T2DM发病风险，其机制尚不十分清楚。肝脏是机体糖脂代谢的重要调节器官，在维持机体血糖和血脂稳态上发挥关键作用。该文系统阐述了NAFLD的发生发展规律和机制，尤其介绍了肝脏糖代谢异常与高血糖之间的关系。NAFLD肝脏通过产生大量的17羟孕酮，增加去泛素化酶USP14基因表达促进糖异生过程，增加肝糖输出，升高血糖。通过改善脂肪肝可有效减少糖尿病的发病风险，对于糖尿病的防治具有重要意义。

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简介：摘要本文报道2例胎儿Pierre Robin序列征（PRS），由胎儿MRI诊断并在引产或生后得以证实。PRS在胎儿MRI上表现为小下颌、舌根后坠、气道变窄及腭裂。MRI诊断PRS有较高的敏感性，可诊断胎儿PRS伴随的结构畸形，给予围生期咨询提供一定指导建议。

简介：摘要本文报道椎管内孤立性纤维性肿瘤2例。该2例患者分别因双下肢无力伴小便失禁2个月余和右下肢麻木半年就诊，MRI上表现为与椎管平行的椭圆形肿块，边界清晰，T1WI呈等信号，T2WI呈等或稍高信号；增强扫描呈明显均匀或不均匀强化。最终术后病理诊断为椎管内孤立性纤维性肿瘤。

简介：摘要椎动脉外伤后出血量大且凶猛，容易被误诊为颈动脉损伤，临床中颈部外伤单纯伤及椎动脉少见，我们诊治2例椎动脉破裂出血患者。患者1，女性，41岁，颈部外伤4 h，探查后行左侧椎动脉吻合+左侧椎前静脉修补+左侧颈内、颈外静脉结扎术，术后10 d患者出现头晕，颅脑MR检查考虑左侧小脑半球脑梗死，椎动脉闭塞、狭窄，应用抗凝药物治疗4个月后头晕症状消失。患者2，女性，28岁，右侧颈部肿胀10 h，数字减影血管造影（DSA）检查示椎动脉起始段假性动脉瘤，介入手术止血困难，暂行颈部填塞后予抗感染治疗，术后4 d行颈部探查+气管切开术，术后18 d再行介入手术，患者出院前气管套管拔除，右上肢肌力0级。

简介：摘要患儿 男，11月龄，以频繁成簇抽搐发作起病，予地西泮、苯巴比妥及丙戊酸钠联合治疗无效，每天抽搐发作数十次，起病第4天因癫痫持续状态入住重症监护病房治疗，并出现嗜睡、意识模糊、不能认人、不自主动作、偶兴奋尖叫、夜间睡眠时间减少，脑电图背景活动慢化，监测到频繁后头部起源的临床发作及电发作，脑脊液抗AMPA2受体IgG抗体阳性，诊断抗AMPA2受体脑炎。予人免疫球蛋白及激素冲击免疫治疗，加用拉考沙胺并减停丙戊酸后抽搐缓解，意识转清。临床上以频繁局灶抽搐发作伴有意识水平下降为主要表现的婴儿，应注意鉴别抗AMPA2受体脑炎，尽早启用免疫治疗改善预后至关重要。

简介：摘要孤立性纤维性肿瘤（SFT）作为一种梭形细胞间叶源性肿瘤，好发于胸膜，也可发生于身体其他部位，其中眼内SFT十分罕见。本文报道2例脉络膜SFT患者，经临床、影像学、组织病理学及免疫组织化学等检查确诊。眼球摘除术后目前均未见复发或转移。

简介：摘要2岁6月龄和10月龄患儿均以排稀水便起病，临床表现为顽固性腹泻、大量水样便、重度营养不良、低蛋白血症，病理示小肠黏膜绒毛萎缩，固有膜淋巴细胞浸润，伴隐窝凋亡，例1血清抗杯状细胞抗体阳性，2例患儿诊断为自身免疫性肠病。该病临床罕见，以营养支持及免疫抑制治疗为主。